Optogenetic control of behavior. Data collected from the slice experiments described above will direct our optogenetic experiments in awake-behaving mice. Using bilateral channel- and halorhodopsin stimulation in vivo, we are presently determining which behavioral tasks are influenced by the selective activation or inhibition of PFC inputs to the VTA. The selective activation of PFC inputs to the VTA neither influences locomotor behavior nor induces a conditioned place preference, but preliminary experiments suggest an impact of this stimulation on reversal learning. Research described below, in Project #2, extends this idea and examines the role of PFC activity in compulsive drug seeking. Overall, the data generated by Project #1 will elucidate the strength of specific neural circuits involving the VTA and NAc. Specific pathways will be examined in their basal state as well as following repeated exposure to cocaine. Drug-induced changes identified in slice experiments will direct our efforts in awake-behaving experiments, where we will use optogenetics to try and counteract drug-induced neural changes and, ultimately, compulsive drug seeking.